Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta

Nat Genet. 2004 May;36(5):528-33. doi: 10.1038/ng1344. Epub 2004 Apr 25.


Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility. Here we show that Cnot7(-/-) males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7(-/-) mice. Transplantation of spermatogonial stem cells from male Cnot7(-/-) mice to seminiferous tubules of Kit mutant mice (Kit(W/W-v)) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7(-/-) condition. The testicular phenotypes of Cnot7(-/-) mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb). We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chromatin Assembly Factor-1
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Female
  • Fibroblasts
  • Gene Expression Regulation*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Oligospermia / complications*
  • Oligospermia / etiology
  • Oligospermia / genetics
  • Phenotype
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / physiology
  • Seminiferous Tubules / metabolism
  • Sperm Motility*
  • Spermatogenesis / genetics
  • Spermatozoa / abnormalities*
  • Stem Cell Transplantation


  • Chromatin Assembly Factor-1
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Rxrb protein, mouse
  • Proto-Oncogene Proteins c-kit